Nonanticoagulant Heparin Inhibits B16F10 Metastasis

Malignant tumor is one of the main disease threatening human health, hematogenous metastasis is a complicated, multi-step process. The formation of tumor cell-platelet emboli complexes in the blood stream is an essential step during metastatic process. In the process of the formation of"microthrombus", plasma protein, adhesion molecules in the cells, especially the selectin and integrin family, play very important roles. Recent results show that fibrinogen, thrombin can mediated the interaction of tumor cells with platelets.Heparin is commonly used as an anti-coagulant in the clinic, and many studies indicate that heparin also inhibits tumor metastasis. However, heparin has not been widely used as an anti-metastasis agent in the clinic due to its side-effect (bleeding) to the patients. In the past, anti-metastasis effect of heparin was thought to correlate with its anti-coagulation activity, but some recent studies find its anti-metastasis effect doesn't completely correlate with its anti-coagulation activity and other bioavailability of heparin may involve in. Some experiments indicate its anti-coagulation activity can be altered by chemical modification. Our experiment shows that the anti-coagulation ability of chemically modified heparins significantly reduce. This study analyzed the anti-coagulation activity and anti-metastasis effect of various chemically modified heparins. It is found that chemically modified heparins RO-heparin and N/2/3DS heparin retain the inhibitory effect on tumor metastasis. Under shear stress condition, heparin and its derivatives lower the number of adhered B16F10 to platelets. Our experiments show that fibrinogen promote the adhesion of B16F10 to platelets to form microthrombus, and heparin and its derivatives inhibit this effect.